The Self-Testing options in the Era of Primary HPV screening for cervical cancer (STEP) trial will evaluate effectiveness of home-based human papillomavirus (HPV) kits for improving cervical cancer screening uptake, cost-effectiveness, and patient and provider experience. STEP is timely in response to 2018 US Preventive Services Task Force cervical cancer screening guidelines, which include HPV testing alone (i,e., primary HPV screening) as a newly recommended option for women aged 30-65 years. Because HPV testing can be performed on clinician- or patient-collected samples (unlike Pap tests), primary HPV screening allows home- based screening options?a potential game changer for delivery of cervical cancer screening. US healthcare systems are keenly interested in identifying cost-effective outreach and patient-centered approaches to reverse declining rates of adherence to guideline-recommended cervical cancer screening. Our central hypotheses are that offering home-based HPV self-collection will increase screening participation, be preferred by women, be cost-effective, and not reduce uptake of other preventive services despite removal of in-clinic screening appointments. We propose a pragmatic randomized controlled trial among 19,026 women ages 30-65 years at Kaiser Permanente Washington who are due for routine cervical cancer screening (oversampling underrepresented minorities) that will compare three outreach approaches: Usual Care (standard patient education and reminders for in-clinic screening); Direct Mail (mailed a home HPV testing kit with information on why it is offered and recommended follow-up for different results); or Opt-In (same information as the direct mail arm with instructions on how to request an HPV kit). Randomization allocation will vary among 3 target populations defined by a woman's prior screening behavior: 1) screening adherent (due now or in the next 12 months); 2) overdue (?6 months past due); and 3) unknown (no recorded screening and recently enrolled). Primary outcomes are screening uptake within 6 months (Aim 1) and cost-effectiveness (Aim 2). Secondary outcomes include: the proportion of women who complete recommended in-clinic follow-up after a positive kit result, uptake of other recommended preventive services (subaim 1), patient and provider preferences about home HPV screening, and facilitators and barriers to follow-up of abnormal results (Aim 3). STEP will be the first US trial to evaluate adherence and cost-effectiveness of different approaches for offering HPV self- sampling for cervical cancer screening. Surveys and in-depth interview data from women and providers will be used with the main trial data to deepen understanding of patient and provider experience with home-based HPV testing. Our trial has tremendous translational potential to improve cervical cancer screening and enable women to receive screening aligned with their preferences. It is timely and directly responsive to calls from US guideline committees to evaluate the effect of HPV self-sampling strategies on screening coverage and follow- up adherence, with the goal of preventing cervical cancer incidence and mortality.